Sunday, June 21, 2009

Antisense drug in combination with paclitaxel for prostate cancer..

I think when I was doing some reference work for my research in 1996, I read about this drug (taxol) [In 1994 the total synthesis has been achieved by Robert Holton of Florida University. He did spend 12 years to achieve the total synthesis because of the assymmtery involved in it [It was after 40 years' after the first exctract from the tree Pacific yew (Taxus brevifolia) has shown anticancer activity and the key ingrediant identified was taxiol]. A diterpenoid, with androgen (a male hormone) blockade chemotherapy has played important role in the treatment of cancer.

Prostate cancer is the second most frequently diagnosed cancer in men after skin cancer. It is estimated there will be 218,890 new cases diagnosed in the U.S. this year(2009). Around 1 in 6 men will develop prostate cancer, a third to a half of whom will recur after local treatment and risk progression to metastatic prostate cancer. Metastatic disease invariably progresses to hormone refractory or castrate resistantprostate cancer (CRPC) if given enough time.

Prostate tumours are initially androgen (male sex hormone) dependent, and can be treated with androgen ablation therapy, however once the disease progresses to its most dangerous and aggressive form, CRPC, treatment options are limited and prognosis is poor. Treatment options depend on disease severity and include radiation and chemotherapy, which are designed to induce programmed cell death (apoptosis) of tumour cells. There is a pressing need for the development of new treatment options.

More interesting and significant results have been achieved by an Australian company (Antisense Therapeutics). i.e., in combination with taxol, antisense drug ATL1101 has yielded good results. ATL1101 is a second generation antisense inhibitor of the insulin-like growth factor-I receptor (IGF-IR) which as reported previously suppressed the growth of human prostate tumors in an animal model of prostate cancer, and slowed down transition to CRPC when used as a single agent.

The research is of great importance because of the fact that in cell culture experiments, the amount of Paclitaxel required to induce tumor cell apoptosis (cell death) was significantly reduced when used in combination with ATL1101. This ability to 'sensitize' tumor cells to the cytotoxic effects of Paclitaxel affirms ATL1101's potential as a chemo-sensitizing agent to be used in combination with existing prostate treatments to improve the outcomes for patients.

I did work for some of the intermediates (ologonucleotides) for ISIS (contract research) and am excited to see that this company has tie up with ISIS. In my opinion as ISIS , is an established company in this field of research, hope soon there will be relief for those patients for whom CRPC, treatment options are limited and prognosis is poor....


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